The Clinicopathological Distinction Between Seropositive and Seronegative Immune-Mediated Necrotizing Myopathy in China

Abstract

Objectives: The present study aimed to compare the clinicopathological features of patients with seronegative immune-mediated necrotizing myopathy (IMNM) and those positive for anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutarylcoenzyme-a reductase (HMGCR) antibodies.Methods: We retrospectively analyzed the data of patients with IMNM treated in the Neurology Department of Tongji Hospital from January 1, 2013, to December 31, 2019.Results: Among the 117 patients with IMNM, 30.8% (36/117) were positive for anti-SRP antibodies, 6.0% (7/117) were positive for anti-HMGCR antibodies, and 13.7% (16/117) were seronegative. Myalgia at presentation (62.5 vs. 23.3%, p = 0.0114) was more commonly observed in patients with seronegative IMNM than in those with seropositive IMNM. Subclinical cardiac involvement was more frequently detected in seronegative IMNM than in seropositive IMNM (6/13 vs. 5/33, p = 0.0509, echocardiogram; 7/7 vs. 12/24, p = 0.0261, cardiac MRI). Deposition of membrane attack complex (MAC) on the sarcolemma of myofibers in biopsied muscle was less commonly observed in patients with seronegative IMNM than in patients with seropositive IMNM (16.7 vs. 68.2%, p = 0.0104). The rate of marked improvement following immunotherapy tended to be higher in patients with seronegative IMNM than in those with seropositive IMNM (87.5 vs. 61%, p = 0.0641).Conclusions: Patients with seronegative IMNM more frequently present with myalgia at onset, exhibit more subclinical cardiac involvement and uncommon MAC deposition on myofibers, and experience better outcomes than those with seropositive IMNM.

Activation of cGAS‐STING pathway – A possible cause of myofiber atrophy/necrosis in dermatomyositis and immune‐mediated necrotizing myopathy

“…Skeletal muscle biopsies obtained from patients with IMNM show prominent myofiber necrosis and regeneration as well as a scarcity of inflammatory infiltrates 35,36 . Necrotic myofibers exhibit the characteristics of different stages of necrotic and regenerating myofibers.…”

“…show prominent myofiber necrosis and regeneration as well as a scarcity of inflammatory infiltrates. 35,36 Necrotic myofibers exhibit the characteristics of different stages of necrotic and regenerating myofibers. In this study, we observed that both atrophic upregulated in IMNM compared with healthy controls.…”

Diagnosis and treatment of statin-induced necrotizing autoimmune myopathy

“…При отсутствии анти-SRP частота интерстициального поражения легких достигала 10-20%, а при их наличии составляла только 5% [8]. Кроме того, наличие этих антител может сопровождаться нарушениями ритма и проводимости [23]. Анти-SRP-позитивный вариант аутоиммунной некротизирующей миопатии характеризуется более частыми экстрамышечными поражениями и дисфагией [4,8].…”

“…В настоящее время данных об особенностях клинической картины СИНАМ в зависимости от серологического варианта недостаточно, так как они были получены при анализе единичных публикаций [14,23]. Тем не менее, результаты серологического исследования позволяют окончательно подтвердить диагноз СИНАМ.…”

Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts

“…Currently, two principle categories of IMNM, anti-signal recognition particle (SRP) autoantibodies-IMNM (SRP-IMNM) and anti-3-hydroxy-3-methylglutaryl-coa reductase (HMGCR) autoantibodies-IMNM (HMGCR-IMNM) (5,6), account for the largest proportion of IMNM and are relatively the most described. Other subtypes, including seronegative IMNM, connective tissue disease-related IMNM, statin-related IMNM, cancer-related IMNM, and immune checkpoint inhibitorsinduced IMNM are also reported (7)(8)(9)(10)(11)(12). The detection of serum anti-SRP autoantibodies in IIM is much earlier than that of anti-HMGCR autoantibodies.…”